神经损伤与功能重建2026，Vol.21Issue(1)：1-6,19,7.DOI:10.16780/j.cnki.sjssgncj.20251428
光遗传学调控TrkA-MAPK/PI3K信号促进iPSC肠神经分化
Optogenetic Control of TrkA-MAPK/PI3K Signaling in iPSC-Derived Enteric Neurogenesis
摘要
Abstract
Objective:To determine whether enteric ganglia regeneration via cell transplantation can ameliorate postoperative bowel dysfunction following conventional surgery and restore normal intestinal function in Hirschsprung disease(HD).Methods:An optogenetic tool was employed to activate TrkA signaling in mouse enteric neural progenitor cells(ENPCs).Downstream signaling activation and ENPC proliferation,migration,and neuronal differentiation were evaluated in vitro.In addition,the effects of optogenetic TrkA activation on ENPC behavior after transplantation were examined.Results:Mouse induced pluripotent stem cell(iPSC)were differentiated into ENPCs expressing Sox 10 and Nestin.ENPCs derived from the HD model exhibited impaired proliferation,migration,and neuronal differentiation.Optogenetic activation of TrkA increased phosphorylation of Erk and Akt,consistent with activation of the MAPK and PI3K pathway.Following transplantation,TrkA activation enhanced ENPC migration and increased expression of the neuronal marker Tuj1.Conclusion:Optogenetic activation of TrkA signaling promotes ENPC migration,proliferation,and neuronal differentiation,supporting a potential strategy for enteric nervous system regeneration in HD.关键词
先天性巨结肠症/光遗传学工具/TrkA信号通路/肠神经再生Key words
Hirschsprung disease/optogenetic tool/TrkA signaling/enteric nervous system regeneration分类
医药卫生引用本文复制引用
王晨萌,黎博,亓俊华,黄泰达..光遗传学调控TrkA-MAPK/PI3K信号促进iPSC肠神经分化[J].神经损伤与功能重建,2026,21(1):1-6,19,7.基金项目
国家自然科学基金(Sox10突变导致Itga4 和 Lama4 表达下调影响神经嵴细胞迁移诱发先天性巨结肠症的机制研究,No.82200562) （Sox10突变导致Itga4 和 Lama4 表达下调影响神经嵴细胞迁移诱发先天性巨结肠症的机制研究,No.82200562）
深圳市科技计划基础研究项目(运用光遗传学工具研究TrkA信号通路调控先天性巨结肠症中肠神经发育的作用与机制,No.JCYJ20210324122809025) （运用光遗传学工具研究TrkA信号通路调控先天性巨结肠症中肠神经发育的作用与机制,No.JCYJ20210324122809025）
深圳市科技计划基础研究项目(胚胎期吸烟暴露对小鼠神经发育影响的研究,No.JCYJ20230807110315031) （胚胎期吸烟暴露对小鼠神经发育影响的研究,No.JCYJ20230807110315031）
